title: Polymorphism of proinflammatory cytokine genes and albuminuria in the Japanese general population: the Takahata study.
abstract: BACKGROUND
  A cluster of proinflammatory cytokines plays an important role in the development of various renal diseases, and the expression of these cytokines is genetically modified. To examine the association between polymorphisms of proinflammatory cytokine genes and albuminuria, a cross-sectional study was conducted in the general population.
  
  
  METHODS
  Single nucleotide polymorphisms (SNPs) in six proinflammatory cytokine genes, including interleukin (IL)-1β, IL-6, IL-8, tumor necrosis factor (TNF)-α, CC chemokine ligand 1 (CCL1) and monocyte chemoattractant protein-1 (MCP-1), were genotyped in 2927 Japanese subjects. Urine albumin-creatinine ratio (UACR) was measured in morning spot urine samples.
  
  
  RESULTS
  Albuminuria (UACR ≥ 30 mg/g) was significantly associated with the A/A + A/G genotype at rs2069852 in the IL-6 gene (P = 0.01) and the A/A genotype at rs228269 in the CCL1 gene (P = 0.002). Multivariate analysis with adjustment for traditional risk factors showed that these genotypes independently predicted albuminuria [odds ratio (OR) 1.782, 95% confidence interval (CI) 1.171-2.712, P = 0.007 for the A/A + A/G genotype at rs2069852 in IL-6, and OR 1.432, 95% CI 1.128-1.770, P = 0.003 for the A/A genotype at rs228269 in CCL1]. The prevalence of albuminuria and the UACR were increased along with the increase of risk genotypes.
  
  
  CONCLUSIONS
  This study revealed that SNPs in the IL-6 and CCL1 genes were associated with albuminuria, and the combination of these genotypes had an additive effect on the prevalence and severity of albuminuria. This indicates that genetic factors influencing inflammatory responses may affect the development of renal injury in the Japanese general population.
authors.affiliation: Department of Cardiology, Pulmonology, and Nephrology, Yamagata University School of Medicine, Yamagata, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Mashima
authors.forename: Tsuneo
authors.initials: T
authors.lastname: Konta
authors.forename: Kosuke
authors.initials: K
authors.lastname: Kudo
authors.forename: Kazuko
authors.initials: K
authors.lastname: Suzuki
authors.forename: Ami
authors.initials: A
authors.lastname: Ikeda
authors.forename: Kazunobu
authors.initials: K
authors.lastname: Ichikawa
authors.forename: Yoko
authors.initials: Y
authors.lastname: Shibata
authors.forename: Tetsu
authors.initials: T
authors.lastname: Watanabe
authors.forename: Gen
authors.initials: G
authors.lastname: Tamiya
authors.forename: Takeo
authors.initials: T
authors.lastname: Kato
authors.forename: Sumio
authors.initials: S
authors.lastname: Kawata
authors.forename: Isao
authors.initials: I
authors.lastname: Kubota
mesh_terms: D000368:Aged; D000419:Albuminuria / Q000235:genetics*; D044466:Asian People / Q000235:genetics; D003430:Cross-Sectional Studies; D016207:Cytokines / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide
chemical_list: D016207:Cytokines